The peptide neurotensin is found in specialized endocrine cells in the gastro-intestinal tract. The peptide is released into the portal circulation in response to mixed micellar solutions of fatty acids and bile salts infused into the intestinal lumen. Since dietary fat both mediates the release of neurotensisn and affects bile salt metabolism, we pose the question of a relationship between neurotensin and bile salt metabolism. The studies we are proposing are designed to determine: 1) whether bile salt micelles stimulate the release of neurotensin; 2) whether neurotensin affects the rate of ileal uptake of bile salts, the hepatic uptake or the biliary secretion rates of bile salts; 3) whether neurotensin release requires the intracellular processing of lipid; 4) whether the specialized endocrine cells in which neurotensin is found are lipid absorbing cells. Solutions of different bile salt species at varying concentrations will be perfused through ileal segments in situ to determine their effect on neurotensin release. The effect of neurotensin on bile salt uptake will be assessed using in situ intestinal segment perfusions, everted gut ring incubations and isolated hepatocyte cultures. Bile salt secretion will be studied in rats with biliary fistulae and the effect of neurotensin during periods of basal and stimulated bile salt secretion examined. Finally, we will study the role of intracellular lipid processing by testingneurotensin release from perfused intestinal segments in the presence and absence of fatty acid binding protein. These studies will provide useful information for understanding the mechanisms relating neurotensin to lipid absorption and bile salt metabolism, thus providing important insights into some physiological roles for neurotensin in the gastrointestinal tract.